Trimethoprim stimulates T-cells through metabolism-dependent and -independent pathways

Sabah El-Ghaiesh, Joseph P. Sanderson, John Farrell, Sidonie N. Lavergne, Wing Kin Syn, Munir Pirmohamed, B. Kevin Park, Dean J. Naisbitt

Research output: Contribution to journalArticlepeer-review

Abstract

Pathways of drug-specific T-cell stimulation have not been fully defined. The aim of this study was to use T-cell clones from a patient hypersensitive to the drug trimethoprim to characterize the involvement of drug metabolism and processing in antigen presentation and cross-reactivity patterns. The MHC-restricted CD4+ and CD8+ T-cell response was dependent on the presence of antigen-presenting cells, and both processing-dependent and -independent pathways of antigen presentation were detected. Stimulation of certain clones was blocked through inhibition of drug-metabolizing enzyme activity. Trimethoprim clones were additionally stimulated with diaveridine and pyrimethamine but not other closely related structures.

Original languageEnglish (US)
Pages (from-to)791-793
Number of pages3
JournalChemical Research in Toxicology
Volume24
Issue number6
DOIs
StatePublished - Jun 20 2011

ASJC Scopus subject areas

  • Toxicology

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